Screening for cancer can be an important means of reducing mortality. To date, randomized controlled trials have provided the most widely accepted means of evaluating the efficacy of screening programs. Case-control studies can potentially provide a time- and cost-efficient alternative approach to prospective evaluations of screening efficacy. However, this approach remains controversial because it has not been thoroughly validated. This doctoral research project will examine the validity of case-control studies of screening efficacy and methodologic problems encountered in their design. Case-control analyses will be performed using the data from the Health Insurance Plan (HIP) of Greater New York randomized controlled trial of breast cancer screening. The benefit of screening in reducing breast cancer mortality will be assessed by comparing the screening histories of 270 women who have died of breast cancer to the screening histories of matched controls who did not die of the disease. The results of these analyses will be compared to the published HIP trial results to assess the validity of the case-control approach. The validity of doing case-control studies in non-randomized settings (e.g., general-population-based studies and studies using screening center data) will be investigated by simulating such studies, using subgroups of HIP trial participants. In addition to these methodologic investigations, several substantive questions regarding screening efficacy which were not answered by the original HIP analyses will be investigated. These include the optimal frequency with which screening should be performed and the efficacy of screening in women under 50 years of age.